What is Wilson’s Disease Wilson’s disease is an inherited disorder in which a…
A Rare Disease Foundation microgrant to Drs. Sylvia Stockler and Clara van Karnebeek enabled these researchers to identify 75 inborn errors of metabolism in children that are treatable if diagnosed early. Based on this study, Dr. Stockler, the Head of the Division of Biochemical Diseases, and other researchers from several different disciplines were awarded the BC Children’s Hospital Foundations’ first Collaborative Area of Innovation grant in April 2011. The goal of this grant is to break down the silos of research and treatment by bringing together clinicians and researchers to collaborate in providing early diagnoses of these and other intellectual disabilities and to develop new treatment strategies. The TIDE Complex Diagnostic Clinic is one of the new innovations developed as part of this grant.
From Rare Disease Report
Researchers at TIDE BC (Treatable Intellectual Disability Endeavor in British Columbia, www.tidebc.org), a group of dedicated clinical scientists at the Children’s Hospital in Vancouver, Canada recently developed a webApp to help diagn ose a total of 81 treatable rare diseases that cause intellectual disability. Led by Drs. Sylvia Stockler and Clara van Karnebeek, the research team developed a means to help doctors identify a small portion of the children who develop intellectual disability for which causal therapy is available – with the potential to prevent brain damage and improve developmental outcome. Their work was recently published in Orphanet Journal of Rare Disease  and Molecular Genetics and Metabolism , and is the first set of studies to dramatically shift the approach in intellectual disability from descriptive to interventional. Their work has been translated into an interactive website at http://www.treatable-id.org/. Recently, Dr. van Karnebeek talked with Rare Disease Report about TIDE BC’s research and clinical successes.
Using standard screening tests more efficiently
Dr. Van Karnebeek has been looking for more efficient ways to determine the etiology of intellectual disability for almost 15 years. Dr. van Karnebeek said, “the causes of this common condition (2.5% of the worldwide population affected) are numerous, thus posing a huge dilemma for physicians. Often these children go from test to test, physician to physician …..without success.” Fortunately, Dr. van Karnebeek was able to team up with the equally passionate Dr. Stockler and they, along with team of researchers at TIDE BC, developed a means to better identify the etiology of patients with intellectual disability. To begin, they have focused on identifying patients with inborn errors in metabolism since they can be fairly easily identified and many can be treated. In an exhaustive literature review, Drs. Stockler and Van Karnebeek identified 81 treatable conditions that can improve the lives of children with intellectual disability .
Dr. van Karnebeek noted that all children brought to TIDE BC are screened for treatable and non-treatable causal conditions so that even if a treatment is not available now, it may be in the future. Furthermore, knowledge of a causal factor can lead to better counseling, management, and prognosis. It may also provide families with new resources if a causal disease is known.
Regarding the 81 treatable inborn errors of metabolism, the team at TIDE BC found that over 65% of these conditions could be identified using group tests; each child with intellectual disability should be screened with these tests. The remaining 35% disorders could be identified with a single disease specific test; the choice of test to perform can be facilitated by the webApp. Once a treatable condition has been identified, the webApp also provides clinicians with a host of evidence based documents to aid in the treatment decision making process (see figure for an example).
Increasing the level of evidence
Although TIDE BC has identified 81 treatable diseases, many of those treatments have not been properly vented with randomized controlled trials. The research team determined that the levels of available evidence for the various treatments were: Level 1 (n=5); Level 2 (n=14); Level 4 (n=45); and Level 4-5 (n=27). Why so many seemingly safe and effective treatments are at low evidence levels is largely due to two limiting factors. First, there are often limited funds to perform such trials in such a small population of patients. Second, many of the conditions have treatment regimens that successfully use vitamins, diets, or nutritional supplements. Since those are not controlled by regulatory agencies, properly designed clinical trials are generally not performed. Unfortunately, it also means that even if those treatments are safe and effective, the level of evidence will always be suspect. On the plus side, TIDE BC is also developing new clinical trial strategies to increase the level of evidence for some of these treatment modalities by collaborating with other clinical researchers on a global scale. Dr. van Karnebeek said, “We are using digital technologies to unite researchers and patients worldwide to participate in trials and share data. Take for example our pyridoxine dependent epilepsy trial – there are impressive pilot study results of lysine restriction as therapy but we now need to perform larger scale study and thus have created a digital registry and website (www.pdeonline.org).”
Making their work accessible to others
While the evidence may be limited, there is no denying that these 81 identifiable disease can be treated and more importantly, those treatments can dramatically alter the outcomes of these children that otherwise may go untreated. www.treatable-id.org the team collaborates with Mr. Roderick Houben, whose company www.health2media.com is dedicated to translating medical knowledge into better care, especially for rare diseases.Knowledge dissemination is a huge obstacle in research for rare diseases; therefore TIDE BC is making optimal use of digital technologies and of the energetic online presence of rare disease families. For their freely available WebAPP at
If you are interested in learning more about treatable inborn errors in metabolism associated with intellectual disability and possibly collaborating with TIDE BC on one of the many ongoing trials, please visit www.tidebc.org.
- van Karnebeek CD, Houben RF, Lafek M, Giannasi W, Stockler S. The treatable intellectual disability APP www.treatable-id.org: A digital tool to enhance diagnosis & care for rare diseases. Orphanet J Rare Dis. 2012;7(1):47.
- van Karnebeek CDM, Stockler S. Treatable inborn errors of metabolism causing intellectual disability: A systematic literature review. Mol Genet Metab. 2012;105(3):368-381.
Treatable rare diseases with randomized clinical trial evidence (level 1)
- Pyrimidine 5-nucleotidase superactivity
- Wilson’s disease
- Niemann-Pick disease type C
- Mucopolysaccharidosis I (MPS I)
- (X-linked) adrenoleukodystrophy
Some of the advocacy groups for the above treatable rare diseases
Possible treatment options for the above treatable rare diseases
- Pyrimidine 5-nucleotidase superactivity: [Uridine supplements]
- Wilson’s disease: [zinc and tetrathiomolybdate; trientine dihydrochloride; Syprine (trientine hydrochloride); Cuprime (penicillamine); Depen (penicillamine)]
- Niemann-Pick disease type C: [(Zavesca (miglustat)] (approved in Canada and other countries for Niemann-Pick type C but in the United States, it is currently only approved for Gaucher disease)]
- Mucopolysaccharidosis I: [Aldurazyme (laronidase)]
- (X-linked) adrenoleukodystrophy: [Stem cell transplantation]
Aug 10 2012 to Aug 12 2012
Aug 16 2012 to Aug 19 2012
Aug 16 2012 to Aug 19 2012
Oct 2 2012
Oct 2 2012